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Biomedical subjects

A S Dofferhoff

Publications and source records attributed to A S Dofferhoff.

At least 19 recordsLinked to original sources

[Intracerebral tuberculomas in a pregnant Somalian woman].

A pregnant Somalian woman aged 28 years, in the Netherlands for the last five years, suffered from a progressive hemiparesis, epilepsia, behavioural problems and low fever. Brain MRI showed multiple lesions with contrast enhancement. Extensive serologic and parasitologic tests on serum and cerebrospinal fluid did not disclose any cause. A brain biopsy revealed only necrosis, but bacterial culture and polymerase chain reaction (PCR) supplied the diagnosis of 'tuberculosis'. PCR on the cerebrospinal fluid remained negative. In the meantime the chest X-ray showed miliary tuberculosis and a spine MRI thoracic spondylodiscitis and a large paravertebral abscess. Subsequently the patient was treated successfully with tuberculostatic agents. Her healthy child which was born by caesarean section was treated with the tuberculostatic agents as well.

Adult↗

Colitis may be part of the antiepileptic drug hypersensitivity syndrome.

PURPOSE: To show that colitis may be part of the antiepileptic hypersensitivity syndrome. METHODS: Description of two case histories. RESULTS: The first patient was a 47-year-old man who developed fever, lymphadenopathy, influenza-like symptoms, facial edema, skin rash and diarrhea after 3 weeks of carbamazepine (CBZ) treatment. Laparotomy because of severe abdominal pain 2 weeks later showed severe colitis with perforations. The second patient was a 41-year-old woman who developed fever, diarrhea, and skin rash 4 weeks after start of CBZ treatment. A colon biopsy confirmed colitis. Stool examinations did not show pathogenic microorganisms, and there was no evidence of Crohn's disease or ulcerative colitis. Both patients had elevated liver enzymes, peripheral eosinophilia, and eosinophils in the infiltrate of the colon. CONCLUSIONS: In view of the close temporal relation between start of CBZ intake and development of colitis, the presence of fever, lymphadenopathy, and rash, and improvement after discontinuation of CBZ, we conclude that the two patients developed an AED hypersensitivity syndrome. Our case histories demonstrate that severe colitis may be part of this syndrome.

Adult↗

Schistosomiasis haematobium as a cause of vulvar hypertrophy.

Schistosomiasis is the most frequently imported helminthic infection in The Netherlands. Patients with Schistosoma haematobium infections usually present with fever, hematuria, dysuria, or urinary frequency. The ectopic localizations in female genital schistosomiasis are frequently misdiagnosed or confounded with sexually transmitted diseases or genital tract cancers. This paper describes a patient who presented with vulvar hypertrophy as a symptom of acute female genital schistosomiasis. The aim of this paper is to draw attention to a neglected parasitic disease that in the future will be encountered in increasing numbers in Western Europe.

Adult↗

Influence of low dose ciprofloxacin on microbial colonization of the digestive tract in healthy volunteers during normal and during impaired colonization resistance.

Ciprofloxacin in low doses is, in volunteers, effective for decontaminating the digestive tract [elimination of aerobic Gram-negative bacilli (GNB)] without disturbing colonization resistance. Before using this concept in neutropenic patients, we investigated if a low dose quinolone is still effective when the colonization resistance is disturbed by another antimicrobial agent. Ciprofloxacin 20 mg daily was effective in eliminating Gram-negative bacilli from the digestive tract in 4/5 volunteers, in 1 volunteer the GNB persisted in low concentration. No colonization with exogenous resistant GNB occurred. Following impairment of colonization resistance by addition of clindamycin 300 mg daily, 3/5 volunteers became colonized by spontaneously acquired exogenous GNB resistant to ciprofloxacin. We conclude that selective decontamination with a quinolone in low dosage cannot be recommended in neutropenic patients because there is, in the case of disturbed colonization resistance, a real risk of acquisition of quinolone-resistant strains.

Adolescent↗

[Systemic fat necrosis and septic arthritis in acute pancreatitis].

Systemic fatty necrosis secondary to acute pancreatitis was diagnosed in a 47-year-old man with high fever and painful nodules on the arms and the upper legs. This was complicated by fatal septic shock, septic arthritis and extensive soft tissue infections with Enterobacter cloacae, which was unsuccessfully treated with several antibiotic regimens, and from which the patient died.

Acute Disease↗

Concentration of pefloxacin in feces during infection prophylaxis in neutropenic patients.

Pefloxacin (400 mg twice daily) was administered orally for infection prophylaxis in neutropenic patients. Diffusible fecal pefloxacin concentration was determined by bioassay during 24 neutropenic periods. The median diffusible fecal pefloxacin concentration was 187 micrograms/g. This concentration was comparable with those found in volunteers following oral and intravenous administration of pefloxacin (400 mg twice daily) (median of 171 and 155 micrograms/g, respectively). From this study, it is concluded that pefloxacin administered orally results in a predictable high diffusible fecal concentration which leads to effective elimination of susceptible aerobic gram-negative bacilli from the colonic flora.

Aged↗

Lactate monitoring with subcutaneous microdialysis in patients with shock: a pilot study.

We describe the use of subcutaneous microdialysis for continuous sampling of lactate to monitor the plasma lactate concentration in eight patients with shock. The dialysate lactate concentrations were significantly correlated with the plasma lactate concentrations (r = 0.8229), but the linear regression lines varied between patients. Therefore, we used the individual regression line of each patient for calibration to calculate estimated plasma values from the dialysate concentrations. While the estimated values were linearly correlated to the plasma lactate values (r = 0.912), the 95% confidence interval of the estimated values was +/- 2.8 mmol/L. Thus, subcutaneous microdialysis does not allow accurate estimation of the plasma lactate concentration. In 3 of the 8 patients, there was a significant negative correlation between the dialysate/plasma lactate ratio and the plasma lactate concentration. This suggests that besides plasma lactate, other factors such as subcutaneous adipose tissue metabolism and blood flow, may influence subcutaneous sampling and dialysate lactate concentration as well. While microdialysis can be used for on-line sampling and continuous monitoring of the concentration of extracellular substances, for the purpose of plasma lactate monitoring, sampling probes should be designed that permit intravascular placement.

Adult↗

[Puerperal toxic shock syndrome caused by Group A beta-hemolytic streptococci].

This case report describes the history of a young female with a streptococcal toxic shock syndrome secondary to a puerperal sepsis. The syndrome was complicated by severe hypotension, reversible kidney dysfunction, adult respiratory distress syndrome, coagulation disturbances, myositis and rhabdomyolysis. This latter complication required amputation of both lower legs.

Adult↗

The release of endotoxin from antibiotic-treated Escherichia coli and the production of tumour necrosis factor by human monocytes.

The influence of antibiotic-induced release of endotoxin from in-vitro grown Escherichia coli on the production of tumour necrosis factor-alpha (TNF) by human monocytes was studied. Antibiotics tested were: cefuroxime (7.5 and 75 mg/L); ceftazidime (10 and 100 mg/L); aztreonam (10 and 100 mg/L); imipenem (10 and 100 mg/L); and tobramycin (8 mg/L). The effect of the combination of cefuroxime plus tobramycin, and the effect of taurolidine, an endotoxin-binding agent, on TNF production was also tested. After incubation for 4 h, all antibiotic-treated cultures (high-dose) induced a similar rise in extracellular TNF production when compared to the controls. However, after incubation for 24 h, a significant rise in TNF production was noticed in the cefuroxime and aztreonam-treated cultures (6440 and 5969 ng/L, respectively) compared to the ceftazidime and imipenem-treated cultures (846 and 381 ng/L, respectively). The cefuroxime-induced release of TNF could be reduced by addition of tobramycin (from 6440 to 1615 ng/L). Similar differences in TNF production were noticed in cell-associated TNF. Dose-response curves did not demonstrate differences in TNF production in aztreonam or imipenem-treated cultures. However, for both cefuroxime and ceftazidime-treated cultures, low-dose treatment resulted in significantly higher production of TNF. The differences in TNF production between these antibiotics could be explained by the production of filaments following treatment with cefuroxime, aztreonam and low-dose ceftazidime, resulting in late bacterial lysis with high levels of endotoxin, whereas treatment with imipenem or high-dose ceftazidime resulted in the formation of spheroplasts, resulting in early lysis of the bacteria and much lower levels of endotoxin. The addition of taurolidine to either imipenem or aztreonam-treated cultures prevented a rise in TNF production as a result of nearly complete neutralization of the released endotoxin. It was concluded that the observed differences in TNF production by human monocytes in vitro were related to differences in the mechanisms and amount of antibiotic-induced release of endotoxin.

Anti-Bacterial Agents↗

Effects of imipenem, cefotaxime and cotrimoxazole on aerobic microbial colonization of the digestive tract.

Superinfections originating from a digestive tract colonized by abnormally high concentrations of aerobic microorganisms as a result of impaired resistance to colonization (CR) may complicate antibiotic therapy. In this study, patients with a moderate to severe systemic infection were randomized to receive either cefotaxime (CTX, n = 10) or cotrimoxazole (CTR, n = 10), 2 antibiotic regimens presumed to spare CR; or imipenem/cilastine (I/C, n = 19). The effect on CR was measured indirectly by comparing the aerobic faecal flora before antibiotic treatment with that on day 8 of treatment. An increase in aerobic faecal flora denotes a disturbed CR, whereas a decrease means that the organism is sensitive to the effective faecal concentration of the antibiotic. Imipenem/cilastine-treated patients showed a significant increase in enterococci and Candida spp., while the number of aerobic Gram-negative rods remained constant. Cefotaxime-treated patients had evidence of an increase in enterococci, but not of Candida spp., and Escherichia coli numbers decreased significantly. In these patients the concentration of other Gram-negative aerobic rods showed a slight increase in 6 patients with a resistant Pseudomonas strain. Cotrimoxazole-treated patients showed a significant decrease in aerobic Gram-negative rods, a significant increase in Candida spp. and no change in enterococci. It is concluded that all 3 antimicrobial agents impair colonization resistance. Whether or not this is followed by overgrowth with resistant micro-organisms depends on the active faecal concentration of the antimicrobial agent and the MIC of the aerobic micro-organisms. The risk of overgrowth of the bowel with resistant Gram-negative bacilli appears to be smaller following cotrimoxazole than following cefotaxime or imipenem/cilastine.

Adult↗

Patterns of cytokines, plasma endotoxin, plasminogen activator inhibitor, and acute-phase proteins during the treatment of severe sepsis in humans.

OBJECTIVE: To study the patterns of plasma concentrations of endotoxin, tumor necrosis factor-alpha (TNF), interleukin-6 (IL-6), plasminogen activator inhibitor-1, C-reactive protein, and serum amyloid A during the treatment of human sepsis. DESIGN: A prospective case series study. SETTING: ICU of the Department of Internal Medicine, University Hospital Groningen, The Netherlands. PATIENTS: Twenty consecutive patients (11 female, 9 male, mean age 67 yrs) with clinically defined sepsis. Eighteen patients were admitted from the outpatient emergency ward; two patients were already inpatients. The control group (n = 7) comprised patients with nonseptic shock. MEASUREMENTS AND MAIN RESULTS: Ten (50%) septic patients had detectable endotoxemia (greater than 5 (ng/L). TNF concentrations on admission were increased in 94% of the septic patients, whereas IL-6 and plasminogen activator inhibitor plasma concentrations were increased in all septic patients. The septic group showed significantly (p less than .05) higher concentrations of TNF, IL-6, plasminogen activator inhibitor-1, C-reactive protein, and serum amyloid A compared with the nonseptic patients. In the septic group, we found a correlation of both IL-6 and plasminogen activator inhibitor concentrations with severity of illness (r2 = .33, p less than .05; r2 = .22, p less than .05, respectively). After the start of antibiotic treatment, high concentrations of TNF and plasminogen activator inhibitor persisted in the nonsurvivors in contrast to decreasing concentrations in most of the survivors. After an initial increase in seven patients, IL-6 concentrations decreased in all septic patients and also in nonsurvivors. CONCLUSIONS: This study confirms previous findings that: a) TNF is a major mediator involved in the pathogenesis of septic shock; b) plasminogen activator inhibitor activity is significantly increased in septic patients and might be involved in the pathogenesis of disseminated intravascular coagulation associated with sepsis; and c) IL-6 is involved in the pathophysiology of septic shock, although further studies are needed to determine whether IL-6 is directly involved in mediating the lethal complications of septic shock or whether it should be considered an "alarm hormone" that reflects endothelial cell injury. Our findings also suggest that the concentrations and trends of these mediators during treatment are valuable for monitoring septic patients.

Acute-Phase Proteins↗

Complement activation and the production of inflammatory mediators during the treatment of severe sepsis in humans.

Sepsis or septic shock is frequently associated with activation of the complement system, coagulation and fibrinolytic changes and the release of several cytokines. In this study we analyzed the relation of complement activation to the inflammatory mediators, hemodynamic and biochemical parameters and severity of illness and outcome in 20 consecutive patients with clinically defined sepsis. Levels of C3a and C3d were elevated in 90% of the patients (median levels 0.19 mg/l and 8.6 mg/l respectively) in comparison to 14% and 42%, respectively of 7 patients with non-septic shock. Levels of C4 were decreased in only 1 of the 20 septic patients. Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, respectively (median levels 122 ng/l and 1300 U/ml) and were clearly interrelated (r = 0.67, p less than 0.01). C3a levels correlated with the APACHE II score (r = 0.57, p less than 0.05) and high C3a levels were associated with fatal outcome (p less than 0.05). C3a was also correlated inversely with mean arterial pressure (r = 0.50, p less than 0.01). Levels of complement C3a and C3d significantly correlated with levels of plasminogen activator inhibitor-1 (PAI) and correlated inversely with AT-III levels. We found no correlation between these complement products and leukocyte counts or lactate levels, nor was there a correlation between C3a or C3d and the cytokines TNF and IL-6. Levels of C3a and C3d did not decrease significantly during the first 24 h of treatment, in contrast to a clear decrease in IL-6 levels in all patients and a decrease in TNF in the surviving patients. TNF levels remained stable or increased in the non-survivors. We conclude that both the complement system and the cytokine system are involved in the pathogenesis of septic shock and may be involved in the development of some of the fatal complications like hypotension and disseminated intravascular coagulation.

Aged↗

Effects of different types and combinations of antimicrobial agents on endotoxin release from gram-negative bacteria: an in-vitro and in-vivo study.

Total and free endotoxin release in time from cultures of Escherichia coli by different antibiotics was studied in vitro for 4 h in relation to the antibiotic effect on viable counts and morphological features of the test cultures. The most rapid fall in viable counts was seen after treatment with imipenem or the combination of imipenem with tobramycin, accompanied by an early, but minimal increase (1.8-fold) of the total (free plus cell-bound) endotoxin level at 1 h. Total endotoxin levels increased approximately 5-fold upon incubation with ceftazidime, tobramycin or the combination of tobramycin with cefuroxime, whereas incubation with cefuroxime or aztreonam alone caused a late 22-and 49-fold increase in total endotoxin, respectively, at 4 h. In chloramphenicol treated cultures there was still an increase in viable counts during therapy, resulting in an ultimately 78-fold increase of mean levels of total endotoxin. Free endotoxin levels increased approximately 6-fold within 1 h upon treatment with imipenem, alone or in combination with tobramycin, or ceftazidime as the result of rapid lysis of bacteria. Treatment with cefuroxime or aztreonam induced a relatively late but much higher release of free endotoxin (118-and 222-fold, respectively), which was due to the formation of long filamentous structures during the first 2 h of incubation and eventually cell lysis. Both tobramycin and the combination of tobramycin with cefuroxime caused a more gradual rise in free endotoxin, with a +/- 15-fold increase in free endotoxin at 4 h. In chloramphenicol treated cultures, as in the control cultures, the level of free endotoxin remained proportional to the amount of viable organisms. We also studied plasma endotoxin levels in 20 patients with septic shock. 10 out of these 20 patients had a detectable endotoxemia (greater than 5 ng/l) on admission. We describe the patterns of plasma endotoxin in these patients during the first 24 h of antibiotic treatment. We conclude that, in the in-vitro study, values of total endotoxin, free endotoxin, and the rate of release of endotoxin varies with the antibiotic used. We also demonstrate that in patients under treatment for septic shock endotoxin release can be related to the administration of antibiotics.

Aged↗